Purpose: Varlitinib is a pan-human epidermal growth factor receptor (HER) inhibitor targeting epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and HER4. We present a phase Ib/II study of a combination of varlitinib and weekly paclitaxel as a second-line treatment for patients with EGFR/HER2 co-expressing advanced gastric cancer (AGC). Materials and Methods: Patients whose tumors with EGFR and HER2 overexpression by immunohistochemistry (≥ 1+) were enrolled. Varlitinib and paclitaxel were investigated every 4 weeks. After determining the recommended phase II dose (RP2D) in phase Ib, a phase II study was conducted to evaluate the antitumor activity. Results: RP2D was treated with a combination of varlitinib (300 mg twice daily) and paclitaxel. Among 27 patients treated with RP2D, the median progression-free survival and overall survival (OS) were 3.3 months (95% confidence interval [CI], 1.7 to 4.9) and 7.9 months (95% CI, 5.0 to 10.8), respectively, with a median follow-up of 15.7 months. Among 16 patients with measurable disease, the objective response rate (ORR) and disease control rate were 31% and 88%, respectively. Patients with strong HER2 expression (n=8) had a higher ORR and longer OS, whereas those with strong EGFR expression (n=3) had poorer outcomes. The most common adverse events (AEs) of any grade were neutropenia (52%), diarrhea (27%), aspartate aminotransferase/alanine transaminase elevation (22%), and nausea (19%). No treatment-related deaths or unexpected AEs resulting from treatment cessation were observed in patients with RP2D. Conclusion A combination of varlitinib and paclitaxel displayed manageable toxicity and modest antitumor activity in patients with EGFR/HER2 co-expressing AGC who progressed after first-line chemotherapy.

Background: Firefighters inevitably encounter emotionally and physically stressful situations at work. Even firefighters without diagnosed post-traumatic stress disorder receive clinical attention because the nature of the profession exposes them to repetitive trauma and high occupational stress. This study investigated gray matter abnormalities related to high occupational stress in firefighters using voxel-based morphometry (VBM) and surface-based morphometry (SBM). Methods: We assessed 115 subjects (112 males and 3 females) using magnetic resonance imaging and evaluated occupational stress by the Korean Occupational Stress Scale-26 (KOSS-26). Subjects were classified into highly or lowly stressed groups based on the median value of the KOSS-26. Results: In VBM analysis, we found that firefighters with high occupational stress had lower gray matter volume (GMV) in both sides of the insula, the left amygdala, the right medial prefrontal cortex (mPFC), and the anterior cingulate cortex than firefighters with low occupational stress. In SBM analysis based on regions of interest, the GMV of the bilateral insula and right mPFC were also lower in the highly stressed group. Within the highly stressed group, low GMV of the insula was significantly correlated with the length of service (left: r = −0.347, P = 0.009; right: r = −0.333, P = 0.012). Conclusion Our findings suggest that regional GMV abnormalities are related to occupational stress. Regional gray matter abnormalities and related emotional dysregulation may contribute to firefighter susceptibility to burnout.

PURPOSE: To evaluate the effect of 0.05% cyclosporine A on the ocular surface after photorefractive keratectomy (PRK). METHODS: This retrospective study included 50 patients who underwent PRK. Patients were divided into two groups: 25 patients in group I were treated with topical 0.05% cyclosporine A with conventional medication, and 25 patients in group II were treated with conventional medication. Visual acuity (VA), tear break-up time (BUT), fluorescein staining score (F-stain), Schirmer I test, and ocular surface disease index (OSDI) were evaluated before surgery and 2 weeks, 1 month, 2 months, and 3 months after surgery. RESULTS: F-stain was significantly lower in group I than in group II at 2 weeks and 1 month (p < 0.05). There was no significant difference in uncorrected VA, BUT, Schirmer I test, or OSDI between the groups. However, group I showed a more effective pattern in dry eye. CONCLUSIONS: Combination treatment with 0.05% cyclosporine A was helpful for early ocular surface stability in patients with dry eye after PRK.
Cyclosporine* ; Fluorescein ; Humans ; Photorefractive Keratectomy* ; Refractive Surgical Procedures ; Retrospective Studies ; Tears ; Visual Acuity

Hepatic ischemia/reperfusion (I/R) injury leads to oxidative stress and acute inflammatory responses that cause liver damage and have a considerable impact on the postoperative outcome. Much research has been performed to develop possible protective techniques. We aimed to investigate the efficacy of SPA0355, a synthetic thiourea analog, in an animal model of hepatic I/R injury. Male C57BL/6 mice underwent normothermic partial liver ischemia for 45 min followed by varying periods of reperfusion. The animals were divided into three groups: sham operated, I/R and SPA0355 pretreated. Pretreatment with SPA0355 protected against hepatic I/R injury, as indicated by the decreased levels of serum aminotransferase and reduced parenchymal necrosis and apoptosis. Liver synthetic function was also restored by SPA0355 as reflected by the prolonged prothrombin time. To gain insight into the mechanism involved in this protection, we measured the activity of nuclear factor-kappaB (NF-kappaB), which revealed that SPA0355 suppressed the nuclear translocation and DNA binding of NF-kappaB subunits. Concomitantly, the expression of NF-kappaB target genes such as IL-1beta, IL-6, TNF-alpha and iNOS was significantly downregulated. Lastly, the liver antioxidant enzymes superoxide dismutase, catalase and glutathione were upregulated by SPA0355 treatment, which correlated with the reduction in serum malondialdehyde. Our results suggest that SPA0355 pretreatment prior to I/R injury could be an effective method to reduce liver damage.
Animals ; Anti-Inflammatory Agents/*therapeutic use ; Benzoxazines/*therapeutic use ; Liver/*drug effects/immunology/*injuries/pathology ; Male ; Mice, Inbred C57BL ; NF-kappa B/immunology ; Reperfusion Injury/*drug therapy/immunology/pathology ; Signal Transduction/drug effects ; Thiourea/*analogs & derivatives/therapeutic use

We presented two interesting cases of gastrocolocutaneous fistula that occurred after percutaneous endoscopic gastrostomy (PEG) tube placement, and its management. This fistula is a rare complication that occurs after PEG insertion, which is an epithelial connection between mucosa of the stomach, colon, and skin. The management of the fistula is controversial, ranging from conservative to surgical intervention. Endoscopists should be aware of the possibility of gastrocolocutaneous fistula after PEG insertion, and should evaluate the risk factors that may contribute to the development of gastrocolocutaneous fistula before the procedure. We reviewed complications of gastrostomy tube insertion, symptoms of gastrocolocutaneous fistula, and its risk factors.
Aged ; Cerebral Infarction/diagnosis ; Digestive System Fistula/*etiology ; Endoscopy, Gastrointestinal ; Enteral Nutrition/*adverse effects/instrumentation ; Gastrostomy ; Humans ; Male ; Middle Aged ; Nervous System Diseases/diagnosis ; Risk Factors ; Tomography, X-Ray Computed

PURPOSE: To evaluate the clinical outcomes of patients with diffractive multifocal toric intraocular lens (IOL) implantation. METHODS: Thirty-four eyes of 26 patients underwent diffractive multifocal toric IOL. Uncorrected visual acuity (UCVA) at distant, intermediate and near and residual refractive astigmatism were measured on the first day, at 2 weeks, and 1, 3 and 6 months postoperatively. Optical quality obtained using the Optical Quality Analysis System II (OQAS II), high-order aberrations (HOA) and patient satisfaction questionnaire were evaluated 3 months postoperatively. RESULTS: At the 6 month postoperative visit, the mean UCVA at distant, intermediate (63 cm, 100 cm) and near were 0.06 +/- 0.07, 0.18 +/- 0.11, 0.16 +/- 0.12 and 0.03 +/- 0.06 (log MAR), respectively. The refractive astigmatism decreased significantly from -1.66 +/- 1.04 D to -0.54 +/- 0.32 D at 6 months postoperatively (p < 0.01). The means of objective scatter index, modulation transfer function (MTF) cut-off value, Strehl ratio and pseudo-accommodation range measured by OQAS II were 1.33 +/- 0.67, 37.24 +/- 9.67 cdp, 0.22 +/- 0.09 and 3.08 +/- 0.53 D, respectively. HOA scores for 5 mm and 6 mm were 0.30 +/- 0.09 and 0.49 +/- 0.15, respectively; 82.3% of the patients were satisfied with the postoperative results, 79.4% of the patients reported they would recommend the procedure to others, and 14.7% of patients reported moderate or severe visual disturbance at night. CONCLUSIONS: Implantation of a diffractive multifocal toric IOL in patients with cataract and corneal astigmatism provided excellent distant, intermediate, and near visual outcomes, good optical quality and high patient satisfaction.
Astigmatism ; Cataract ; Cytidine Diphosphate ; Humans ; Lens Implantation, Intraocular* ; Lenses, Intraocular ; Patient Satisfaction ; Surveys and Questionnaires ; Visual Acuity

PURPOSE: The present study evaluated the changes in tear film, cornea and ocular surface according to the duration of soft contact lens wear. METHODS: A total 65 patients with 130 eyes were enrolled the present study, and were divided into 4 grous. The control group (group A) was composed of 32 eyes of 16 patients who had not worn soft contact lenses, group B, (34 eyes of 17 patients), had worn soft contact lenses less than 5 years, group C, (32 eyes of 16 patients), had worn soft contact lenses for 5 to 10 years and group D, (32 eyes of 16 patients), had worn soft contact lenses for more than 10 years. The tear break-up time (BUT), Schirmer's test, corneal sensitivity test, central corneal thickness, ocular surface disease index (OSDI), corneal fluorescein staining score, specular microscopy and conjunctival impression cytology were analyzed. The results were compared between the control group and the soft contact lens groups. RESULTS: In group B, BUT significantly decreased, but corneal fluorescein staining score and squamous metaplasia significantly increased (p < 0.05). In group C, OSDI and snake-like chromatin pattern significantly increased, but corneal thickness and goblet cell density significantly decreased (p < 0.05). In group D, the coefficient of variation for endothelium significantly increased, but corneal sensitivity and hexagonality significantly decreased (p < 0.05). CONCLUSIONS: Duration of soft contact lens wear influences changes in tear film, cornea and ocular surface.
Chromatin ; Contact Lenses, Hydrophilic ; Cornea ; Endothelium ; Eye ; Fluorescein ; Goblet Cells ; Humans ; Metaplasia ; Microscopy ; Tears

PURPOSE: To report the clinical results after the implantation of intrastromal corneal ring segments (Intacs(R)) by manual tunnel creation for the correction of keratoconus. METHODS: This retrospective case series was comprised of 10 eyes of 8 consecutive keratoconic patients. Visual acuity, refractive outcome, keratometric values, anterior chamber depth, central corneal thickness, and endothelial cell density were evaluated before and at 1 month, 3 months, and 6 months postoperatively. In addition, the implanted ring segment depth was measured by anterior segment optical coherence tomography at postoperative 6 months. Any postoperative complications were also recorded. RESULTS: Visual acuity was improved in 9 out of 10 eyes. Spherical equivalent and keratometric values were decreased in all eyes. There was no significant difference in central corneal thickness, but endothelial cell density and anterior chamber depth were slightly decreased. The depth of ring segments was almost constant at superior, middle, and inferior. There was a single case of descented implanted ring segments and 6 cases of stromal infiltration around ring segments, but visual acuity was unaffected. In addition, 1 case showed implanted ring exposure, thus the superior ring segment was removed at postoperative 4 months. CONCLUSIONS: Intrastromal corneal ring segment implantation (Intacs(R)) by manual tunnel creation appears to be effective in improving the visual acuity and stabilizing corneal refractive power in keratoconic patients.
Anterior Chamber ; Endothelial Cells ; Eye ; Humans ; Keratoconus ; Postoperative Complications ; Retrospective Studies ; Tomography, Optical Coherence ; Visual Acuity

PURPOSE: To describe a case of bilateral acute myopia and acute angle-closure associated with phentermine hydrochloride, a drug used for obesity treatment. CASE SUMMARY: A 25-year-old woman visited our hospital with blurry vision and ocular pain after taking phentermine hydrochloride for three weeks. Manifest refraction accompanied myopic shift in the both eyes, slit-lamp examination showed forward displacement of the lens-iris diaphragm and fundus examination revealed retinal folds. Suspecting phentermine hydrochloride induced acute myopia and acute angle closure, discontinuation of the drug and administration of cycloplegic agents and antiglaucomatic agent successfully resolved the symptoms. CONCLUSIONS: Although the exact mechanism is unknown, phentermine hydrochloride may generate ciliochoroidal effusion and ciliary edema, lead to acute myopia and acute angle closure resulting from forward displacement of the lens-iris diaphragm.
Adult ; Diaphragm ; Displacement (Psychology) ; Edema ; Eye ; Female ; Humans ; Myopia ; Obesity ; Phentermine ; Retinaldehyde ; Vision, Ocular

Vertigo due to primary cardiac disease, known as cardiogenic vertigo, has been rarely reported. We report one case showing recurrent vertigo episodes due to sick sinus syndrome. A 77-year-old female presented to our department because of long history of intermittent brief episodes of rotatory vertigo and non-vertiginous dizziness. She had no past medical history. There was no abnormal sign in neurological examination. Cardiac murmur, finally confirmed as grade 4 ejection systolic and grade 3 decrescendo diastolic murmurs, was found on physical examination. Brain magnetic resonance imaging and auditory evoked potential did not show any abnormal findings. She was consulted to a cardiologist for the evaluation of cardiac murmur. After the evaluation using electrocardiogram, echocardiography, and holter monitoring, she was diagnosed as sick sinus syndrome. After then, a ventricle ventricle inhibited (VVI) pacemaker was inserted. She did not complain of vertigo and dizziness for 3 months after the insertion of a VVI pacemaker. This case shows the need of auscultation for patients with recurrent vertigo episodes although there is rare cardiogenic vertigo.
Aged ; Auscultation ; Brain ; Dizziness ; Echocardiography ; Electrocardiography ; Electrocardiography, Ambulatory ; Evoked Potentials, Auditory ; Female ; Heart Diseases ; Heart Murmurs ; Humans ; Magnetic Resonance Imaging ; Neurologic Examination ; Physical Examination ; Sick Sinus Syndrome ; Vertigo